RESUMO
Undergraduate medical students who participate in community outreach programs gain a multitude of benefits that impact not only their professional development but also the well-being of the communities they serve. At the Virginia Tech Carilion School of Medicine (VTCSOM), students have the opportunity to volunteer in the "Bodies and Bites" program at the West End Center for Youth, an after-school educational center that serves K-12 children in Roanoke, Virginia. The purpose of Bodies and Bites is to teach elementary school children in 2nd to 5th grade how their bodies work and how to keep them healthy through good nutrition and exercise. All sessions are led by VTCSOM medical students and graduate students from our partnering academic institution, the Fralin Biomedical Research Institute (FBRI). Each week, the children and Health Professions students explore a different topic related to human anatomy and physiology using anatomical models, small group discussions, and hands-on activities. At the end of each session, the participants create a healthy snack related to the day's topic. The overall goal of the present study was to assess the perception of the Bodies and Bites program from the view of our student volunteers, and the 4th and 5th graders who attend the West End Center. Now in its 6th year, Bodies and Bites continues to be popular as a voluntary program among our Health Professions students, and is well received by the West End Center and the elementary school children they serve. Our students and community mutually benefit from this program, with the former having an opportunity to briefly disengage from the rigors of their studies while gaining valuable skills in science communication and inspiring children to pursue fields in Science, Technology, Engineering, Math, and Medicine (STEMM), and the latter having fun while learning about their bodies and discovering ways to improve their health.
Assuntos
Anatomia , Humanos , Criança , Virginia , Anatomia/educação , Faculdades de Medicina , Feminino , Masculino , Fisiologia/educação , Estudantes de Medicina/estatística & dados numéricosRESUMO
Antipsychotic-induced dopamine supersensitivity, or behavioral supersensitivity, is a problematic consequence of long-term antipsychotic treatment characterized by the emergence of motor abnormalities, refractory symptoms, and rebound psychosis. The underlying mechanisms are unclear and no approaches exist to prevent or reverse these unwanted effects of antipsychotic treatment. Here we demonstrate that behavioral supersensitivity stems from long-lasting pre, post and perisynaptic plasticity, including insertion of Ca2+-permeable AMPA receptors and loss of D2 receptor-dependent inhibitory postsynaptic currents (IPSCs) in D2 receptor-expressing medium spiny neurons (D2-MSNs) in the nucleus accumbens core (NAcore). The resulting hyperexcitability, prominent in a subpopulation of D2-MSNs (21%), caused locomotor sensitization to cocaine and was associated with behavioral endophenotypes of antipsychotic treatment resistance and substance use disorder, including disrupted extinction learning and augmented cue-induced cocaine-seeking behavior. Chemogenetic restoration of IPSCs in D2-MSNs in the NAcore was sufficient to prevent antipsychotic-induced supersensitivity, pointing to an entirely novel therapeutic direction for overcoming this condition.
Assuntos
Antipsicóticos , Cocaína , Antipsicóticos/farmacologia , Cocaína/farmacologia , Núcleo Accumbens/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismoRESUMO
CONTEXT.: Delta-like protein 3 (DLL3) is a protein that is implicated in the Notch pathway. OBJECTIVE.: To present data on DLL3 prevalence in small cell lung cancer and staining characteristics of the VENTANA DLL3 (SP347) Assay. In addition, the assay's immunoreactivity with other neoplastic and nonneoplastic tissues is outlined. DESIGN.: Individual formalin-fixed, paraffin-embedded specimens of small cell lung cancer and tissue microarrays comprising neoplastic and nonneoplastic tissues were procured. Sections were cut and stained with DLL3 (SP347) assay. The slides were examined to determine prevalence, staining characteristics, and immunoreactivity. RESULTS.: Cytoplasmic and/or membranous staining was observed in 1040 of 1362 specimens of small cell lung cancer (76.4%). Homogenous and/or heterogeneous and partial and/or circumferential granular staining with varied intensities was noted. Immunoreactivity was also observed in other neoplastic and nonneoplastic tissues. CONCLUSIONS.: Our study findings provided the profile of DLL3 staining characteristics that can be used for determining the level of DLL3 expression in small cell lung cancer.
Assuntos
Anticorpos Monoclonais/imunologia , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Membrana/metabolismo , Carcinoma de Pequenas Células do Pulmão/patologia , Animais , Estudos de Coortes , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/diagnóstico , Inclusão em Parafina , Coelhos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Análise Serial de TecidosRESUMO
With current technology, tissue-engineered skeletal muscle analogues (bioartificial muscles) generate too little active force to be clinically useful in orthopaedic applications. They have been engineered genetically with numerous transgenes (growth hormone, insulinlike growth factor-1, erythropoietin, vascular endothelial growth factor), and have been shown to deliver these therapeutic proteins either locally or systemically for months in vivo. Bone morphogenetic proteins belonging to the transforming growth factor-beta superfamily are osteoinductive molecules that drive the differentiation pathway of mesenchymal cells toward the chondroblastic or osteoblastic lineage, and stimulate bone formation in vivo. To determine whether skeletal muscle cells endogenously expressing bone morphogenetic proteins might serve as a vehicle for systemic bone morphogenetic protein delivery in vivo, proliferating skeletal myoblasts (C2C12) were transduced with a replication defective retrovirus containing the gene for recombinant human bone morphogenetic protein-6 (C2BMP-6). The C2BMP-6 cells constitutively expressed recombinant human bone morphogenetic protein-6 and synthesized bioactive recombinant human bone morphogenetic protein-6, based on increased alkaline phosphatase activity in coincubated mesenchymal cells. C2BMP-6 cells did not secrete soluble, bioactive recombinant human bone morphogenetic protein-6, but retained the bioactivity in the cell layer. Therefore, genetically-engineered skeletal muscle cells might serve as a platform for long-term delivery of osteoinductive bone morphogenetic proteins locally.
Assuntos
Proteínas Morfogenéticas Ósseas/genética , Mioblastos Esqueléticos/citologia , Mioblastos Esqueléticos/fisiologia , Transgenes/fisiologia , Fosfatase Alcalina/metabolismo , Animais , Proteína Morfogenética Óssea 6 , Linhagem Celular , Células Cultivadas , Imuno-Histoquímica , Ortopedia , Fenótipo , Engenharia Tecidual , Transdução GenéticaRESUMO
Human bioartificial muscles (HBAMs) are tissue engineered by suspending muscle cells in collagen/MATRIGEL, casting in a silicone mold containing end attachment sites, and allowing the cells to differentiate for 8 to 16 days. The resulting HBAMs are representative of skeletal muscle in that they contain parallel arrays of postmitotic myofibers; however, they differ in many other morphological characteristics. To engineer improved HBAMs, i.e., more in vivo-like, we developed Mechanical Cell Stimulator (MCS) hardware to apply in vivo-like forces directly to the engineered tissue. A sensitive force transducer attached to the HBAM measured real-time, internally generated, as well as externally applied, forces. The muscle cells generated increasing internal forces during formation which were inhibitable with a cytoskeleton depolymerizer. Repetitive stretch/relaxation for 8 days increased the HBAM elasticity two- to threefold, mean myofiber diameter 12%, and myofiber area percent 40%. This system allows engineering of improved skeletal muscle analogs as well as a nondestructive method to determine passive force and viscoelastic properties of the resulting tissue.